| First Author | Nguyen TT | Year | 2007 |
| Journal | Reproduction | Volume | 134 |
| Issue | 1 | Pages | 41-9 |
| PubMed ID | 17641087 | Mgi Jnum | J:123298 |
| Mgi Id | MGI:3717962 | Doi | 10.1530/REP-06-0087 |
| Citation | Nguyen TT, et al. (2007) IGF-I and insulin activate mitogen-activated protein kinase via the type 1 IGF receptor in mouse embryonic stem cells. Reproduction 134(1):41-9 |
| abstractText | Although IGF-I and insulin are important modulators of preimplantation embryonic physiology, the signalling pathways activated during development remain to be elucidated. As a model of preimplantation embryos, pluripotent mouse embryonic stem cells were used to investigate which receptor mediated actions of physiological concentrations of IGF-I and insulin on growth measured by protein synthesis. Exposure of mouse embryonic stem (ES) cells to 1.7 pM IGF-I or 1.7 nM insulin for 4 h caused ~25% increase in protein synthesis when compared with cells cultured in basal medium containing BSA. Dose-response studies showed 100-fold higher potency of IGF-I that pointed to the type 1 IGF receptor as the mediating receptor for both ligands. This was confirmed using an anti-type 1 IGF receptor-blocking antibody (alphaIR3). Both 1.7 pM IGF-I and 1.7 nM insulin increased phosphorylation of the type 1 IGF receptor and this increase was blocked by alphaIR3, but the insulin receptor was not phosphorylated. Finally, binding of either agonist led to downstream phosphorylation of ERK1/2 mitogen-activated protein kinase (MAPK) also via IGF-1R as this was blocked by alphaIR3. Together, these results suggest that IGF-I and insulin modulate ES cell physiology through binding to the type 1 IGF receptor and subsequent activation of MAPK pathway. |
